Surgical Biopsy Research Articles

Magnetic Resonance Imaging Texture Analysis Based on Intraosseous and Extraosseous Lesions to Predict Prognosis in Patients with Osteosarcoma

Objectives: To construct an optimal magnetic resonance imaging (MRI) texture model to evaluate histological patterns and predict prognosis in patients with osteosarcoma (OS). Methods: Thirty-four patients underwent pretreatment MRI and were diagnosed as having OS by surgical resection or biopsy between September 2008 and June 2018. Histological patterns and 3-year survival were recorded. Manual segmentation was performed in intraosseous, extraosseous, and entire lesions on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted images to extract texture features and perform principal component analysis. A support vector machine algorithm with 3-fold cross-validation was used to construct and validate the models. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate diagnostic performance in evaluating histological patterns and 3-year survival. Results: Eight patients were chondroblastic and the remaining twenty-six patients were non-chondroblastic patterns. Twenty-seven patients were 3-year survivors, and the remaining seven patients were non-survivors. In discriminating chondroblastic from non-chondroblastic patterns, the model from extraosseous lesions on the T2-weighted images showed the highest diagnostic performance (AUCs of 0.94 and 0.89 in the training and validation sets). The model from intraosseous lesions on the T1-weighted images showed the highest diagnostic performance in discriminating 3-year non-survivors from survivors (AUCs of 0.99 and 0.88 in the training and validation sets) with a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 92.6%, 75.0%, and 96.2%, respectively. Conclusions: The texture models of extraosseous lesions on T2-weighted images can discriminate the chondroblastic pattern from non-chondroblastic patterns, while the texture models of intraosseous lesions on T1-weighted images can discriminate 3-year non-survivors from survivors.

Zoonotic Dirofilaria sp. "hongkongensis" in subcutaneous nodules from dogs and cats, Hong Kong SAR.

Dirofilaria sp. "hongkongensis" is a putative Dirofilaria species, initially identified in subcutaneous nodules in humans in Hong Kong and in other South and Southeast Asian regions. While it differs genetically from the better-known zoonotic species, Dirofilaria repens and Dirofilaria immitis, information on the lesions caused by Dirofilaria sp. "hongkongensis" in the hosts as well as on its biology is scarce. This study documents for the first time the presence of this filarioid nematode in subcutaneous nodules in dogs and cats in Hong Kong, where it was originally described in human patients, therefore providing evidence for the zoonotic nature of this parasite. Records of Veterinary Diagnostic Laboratory of City University of Hong Kong were searched between 2019 and 2024 for histological reports of possible filarioid-associated lesions. Tissue samples were collected by excisional surgical biopsy and processed with routine paraffin techniques. Selected slides were stained using various staining techniques [i.e., hematoxylin and eosin, periodic acid-Schiff (PAS), Grocott methenamine silver (GMS) or Ziehl-Neelsen (ZN) and Gram stain]. DNA from formalin-fixed paraffin-embedded tissue were extracted, submitted to conventional polymerase chain reaction (cPCR) and sequencing (i.e., cox1 and 12S rRNA genes) and phylogenetic analyzed. A total of five subcutaneous nodules from four cats and one from a dog with histopathology suggestive of filariosis were selected. The presence of Dirofilaria sp. "hongkongensis" was morphologically and molecularly confirmed in one dog and one cat. Both histopathological presentation and phylogenetic analysis enabled classification of this species close to D.repens and within the subgenus Nochtiella. In the remaining three cases, one showed histological evidence of aberrant nematode migration, while non-parasitic causes were identified in the other two. This study provides the first evidence of Dirofilaria sp. "hongkongensis" in subcutaneous nodules in cats and dogs. The histology of clinical lesions of this filarioid species herein described is closely related to those caused by D.repens. Overall, this species should be considered in differential diagnoses of subcutaneous lesions in both animals and humans in the region.

Challenging case of disseminated tuberculosis in an immunocompetent adult.

Disseminated tuberculosis (TB) is a TB infection involving two or more noncontiguous sites. It is a challenging medical care due to its misleading presentation. Although it is associated with immunodepression, rare cases have been described in immunocompetent patients.We report the case of a 27-year-old immunocompetent man who presented with an altered general condition and dyspnea. Chest computed tomography (CT) revealed pulmonary masses and mediastinal lymphadenopathy. Sputum smear microscopy for acid-fast bacilli was negative. Scannoguided transparietal lung biopsy was performed twice with inflammatory tissue in histological study. A surgical lung biopsy was then made. The histopathology report confirmed TB involving lung, pleura and lymph nodes. A few days after antituberculosis therapy was started, the patient developed psychomotor slowing related to quadriportal hydrocephalus. He benefited from ventriculoperitoneal bypass. Polymerase chain reaction for detection of Mycobacterium TB was positive in cerebrospinal fluid.In conclusion: The diagnosis of disseminated TB is challenging owing to its non-specific clinical and radiological presentation and the frequent negativity of biological fluids for tubercle bacilli. Molecular biology should always be considered in front of lingering symptoms, particularly in endemic areas, given their speed and sensitivity, thus avoiding invasive diagnostic procedures, as was the case with our patient.

Abstract B011: Circulating tumor DNA profiling in colorectal cancer to detect guideline-based targeted mutations at a Quebec health care center

Abstract Liquid biopsy is an emerging tool in oncology, providing minimally invasive detection of tumor- specific DNA in body fluids, known as circulating tumor DNA (ctDNA). Colorectal cancer (CRC) has shown a high rate of shedding of ctDNA, making it a promising prognostic and possibly predictive biomarker in the personalized management of patients with CRC. Therefore, the half-life of ctDNA in circulation is estimated to be between 16 minutes and several hours, indicating a need for rapid processing. This study aimed to explore the concordance between the mutational profiles in tumor tissue and ctDNA from plasma obtained using EDTA tubes as well as the correlation between ctDNA and disease stage, to evaluate the potential of implementing liquid biopsy testing in CRC cases, following biobank standards. In this retrospective cohort, 58 patients with CRC stage T1 to T4 were enrolled at the Research Institute McGill University Health Centre (RI-MUHC). Tumor tissue was obtained through surgical resection or biopsies of formalin-fixed paraffin-embedded tissue, and blood samples were drawn pre-surgery using EDTA tubes. Cell-free DNA (cfDNA) was extracted from 1-2mL plasma samples using QIAamp Circulating Nucleic Acids. Next-Generation Sequencing using a 52-gene (AmpliSeq for Illumina Focus Panel) was performed to identify the tumor mutations and subsequently droplet digital PCR (ddPCR) was performed to identify the plasma mutations. Among the 58 patients, the mean age was 62 years (range 29-86), and 29 were women. Forty- one patients had left-sided tumor. At least 1 tumor-specific mutation was detected in all tissue tumor samples. Overall, the most frequently identified mutations in this cohort were: BRAF V600E (22.4%), KRAS G12D (12.1%), KRAS G12V and KRAS G13D (8.6%). Cell-free DNA was obtained from 32 patients and showed a mean concentration of 975 ng/mL (range 400- 1,995) for stage T1, 584 ng/mL (range 228-1,300) for stage T2, 1,127 ng/mL (range 249-4,160) for stage T3 and 2,083 ng/mL (range 860-3,680) for stage T4. ddPCR revealed mutation concordance between ctDNA and matched tumor tissue of 28.1%. When tumors were stratified by stage, the concordance was 0% (n=0/3) in patients with T1 tumors, 16.7% (n=1/6) in patients with T2 tumors, 25% (n=5/20) in patients with T3 tumors and 100% (3/3) in patients with T4 tumors. This study showed that ctDNA detection of mutations has excellent concordance in stage T4 tumors, highlighting the potential of ctDNA in advanced stage disease. However, in T1-3 tumor stages the concordance was low, showing the importance of preanalytical steps such as the use of cell-free DNA preservative tubes for sensitive and accurate detection of ctDNA in patients with earlier stage disease. Citation Format: Monyse de Nobrega, Kyle Dickinson, Saba Alsaddah, Alexandra Bartolomucci, Tadhg Ferrier, Anne Mahalia Olivier Mahalia Olivier, Mina Farag, Gertuda Evaristo, Sophie Camilleri-Broet, Andrea Gomez, Thupten Tsering, Lawrence Lee, Pierre Olivier Fiset, Julia V. Burnier. Circulating tumor DNA profiling in colorectal cancer to detect guideline-based targeted mutations at a Quebec health care center [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B011.

A novel electrochemiluminescent cytosensor using dual-target magnetic probe recognition and nanozymes-catalyzed cascade signal amplification for precise phenotypic enumeration of CTCs.

The inability of surgical biopsy to monitor the dynamic evolution of cancer cells hampers its capacity to reflect real-time tumor heterogeneity. Circulating tumor cells (CTCs), as a crucial target in liquid biopsy, offer a novel approach for accurate monitoring of tumors. However, the rarity and complex phenotype resulting from epithelial-mesenchymal transition pose challenges for conventional methods such as CellSearch and immunohistochemistry, which have insufficient ability for simultaneous phenotyping and enumeration of CTCs. The enumeration of a single phenotype CTCs is insufficient for accurately assessing disease progression. Herein, we propose a strategy to address this issue by fabricating an electrochemiluminescence cytosensor via the integration of dual-target enrichment and nanozymes-catalyzed cascade signal amplification. The graphene oxide@hollow mesoporous Prussian blue/Pt (GO@HMPB/Pt) complex, possessing a large specific surface area and exceptional catalytic activity, is employed for loading a substantial amount of luminol as the signal probe. Dual-target magnetic PPy@Fe3O4/Au-antibody/aptamer is utilized for the magnetic capture of both epithelial and interstitial CTCs. Glutathione (GSH) can disrupt theAu-S bond on aptamer by a thiol exchange reaction and selectively releases a specific subset of phenotypic CTCs, thereby facilitating the efficient capture, accurate classification, and ultrasensitive detection of CTCs in peripheral blood. Using the epithelial MCF-7 and mesenchymal Hela cells as models, the ECL cytosensor demonstrates excellent performance in identifying cells spiked into whole blood. This study presents a novel approach for early detection of metastasis, tracking tumor recurrence, and monitoring therapeutic efficacy.

CTNI-15. A PERIOPERATIVE STUDY OF SAFUSIDENIB IN PATIENTS WITH IDH1 MUTATED GLIOMA

Abstract BACKGROUND IDH mutations cause aberrant accumulation of (R)-2-hydroxyglutarate (2-HG), an oncometabolite that promotes tumorigenesis through abnormal hypermethylation of histones and DNA as well as suppression of normal cellular differentiation. IDH inhibition significantly improves progression free survival in patients with IDH mutant WHO grade 2 glioma, however most patients progress, and there is a lack of understanding on mechanistic reasons for failure. METHODS We tested Safusidenib, an oral, blood brain barrier penetrant IDH1 R132X enzyme inhibitor in a single arm, open label perioperative study. Patients with IDH1 mutated glioma, treatment naïve to radiation or chemotherapy, received Safusidenib (250 mg BID) for four weeks following surgical biopsy and prior to definitive resection (Part A). After resection patients continued Safusidenib until toxicity or progression (Part B). Translational endpoints include paired whole genome transcriptome sequencing (WGTS), single nuclei RNA sequencing (snRNAseq), spatial transcriptomics and spatial metabolomics as well as longitudinal sampling of blood and CSF for circulating tumour DNA (ctDNA). Here we are reporting Part A of the study. RESULTS As of May/27/2024 10 patients (mean age 37, 40% female) have been enrolled: seven with astrocytoma, three with oligodendroglioma; six had prior surgical resection. Pharmacokinetic sampling showed a mean tumor concentration 2457 ng/mL (range 957.0 – 4810) with tumor:plasma ratio 0.33. Consistent with mechanism, tumor 2-HG reduced 86% from biopsy (mean 75.0μM, range 7.8-203) to surgery (10.3μM, range 2.3 – 30.8), as well as identification of novel biomarkers of response. Paired tumour snRNAseq reveals transcriptional shift with changing cell-to-cell communication, and increased immune infiltration post-treatment, validated by spatial transcriptomics. Additionally, we find reduced heterogeneity consistent with a more differentiated tumour state. Treatment was well tolerated with ongoing follow-up. CONCLUSIONS This innovative trial facilitates intra-patient comparisons and confirmation of the on-target effects of Safusidenib, enhancing understanding of the mechanisms of response and resistance. The approach serves as a proof of concept for advancing drug development in glioma through perioperative trials.

Using Deep Learning, Optuna, and Digital Images to Identify Necrotizing Fasciitis

Necrotizing fasciitis, which is categorized as a medical and surgical emergency, is a life-threatening soft tissue infection. Necrotizing fasciitis diagnosis primarily relies on computed tomography (CT), magnetic resonance imaging (MRI), ultrasound scans, surgical biopsy, blood tests, and expert knowledge from doctors or nurses. Necrotizing fasciitis develops rapidly, making early diagnosis crucial. With the rapid progress of information technology and systems, in terms of both hardware and software, deep learning techniques have been employed to address problems in various fields. This study develops an information system using convolutional neural networks (CNNs), Optuna, and digital images (CNNOPTDI) to detect necrotizing fasciitis. The determination of the hyperparameters in convolutional neural networks plays a critical role in influencing classification performance. Therefore, Optuna, an optimization framework for hyperparameter selection, is utilized to optimize the hyperparameters of the CNN models. We collect the images for this study from open data sources such as Open-i and Wikipedia. The numerical results reveal that the developed CNNOPTDI system is feasible and effective in identifying necrotizing fasciitis with very satisfactory classification accuracy. Therefore, a potential future application of the CNNOPTDI system could be in remote medical stations or telemedicine settings to assist with the early detection of necrotizing fasciitis.

PATH-01. SELLAR SOLITARY FIBROUS TUMORS WHO GRADE II AND III: MIMICS OF NON-FUNCTIONING PITUITARY ADENOMAS

Abstract Solitary fibrous tumors WHO grade II and III (SFTs II/III) are rare mesenchymal neoplasia accounting for 0.4% of primary central nervous system tumors. SFTs II/III located in the sella turcica region are even rarer and, since the first case described in 1983, only 21 case reports of sellar/suprasellar SFTs II/III (ssSFTs II/III) have been described to this day. We aim to analyze ssSFTs II/III and to demonstrate that can be differentiated from non-functioning pituitary adenomas through pathological examination alone. We analyzed 20 case reports of ssSFTs II/III identified through PubMed and Google searches and a new unpublished case presented at Emory University. ssSFTs II/III are equally represented in both sexes, with 11 cases over 21 occurring in females and the mean age of onset at 46 years old. Clinically, ssSFTs II/III present with compression symptoms related to the tumor location. Headache, visual field defects, and anterior hypopituitarism-related symptoms are frequent chief complaints. As such, almost all cases of ssSFTs II/III had a pre-biopsy working diagnosis of non-functioning pituitary adenomas. The differentiation between SFTs II/III and pituitary adenomas based on imaging findings remains challenging, and surgical biopsies are necessary for a definitive diagnosis. ssSFTs II/III surgical reports describe a unifying trait of a highly vascular tumor adherent to the dura that bleeds profusely after resection. These characteristics are less consistent with a pituitary adenoma. The genetic hallmark of SFTs at all anatomical sites is paracentric inversions at 12q13, fusing the NAB2 and STAT6 genes, with consequent overexpression of STAT6. Pituitary adenomas lack this genetic signature. ssSFTs II/III have an overlapping presentation and similar imaging findings of pituitary adenomas, but different management and prognosis. Hence, it is crucial to include ssSFTs II/III among the pre-biopsy differential of sellar/suprasellar masses identified on imaging. Pathology confirmation is required to guide therapy.

DDEL-05. IMPRESSIVE RESPONSE TO IDH-INHIBITOR THERAPY IN IDH-MUTANT, H3K27M INTACT BRAINSTEM GLIOMAS

Abstract IDH-mutated brainstem gliomas in adults are a rare entity, with only a handful of cases reported in the literature. Diagnosis and treatment of these gliomas remain challenging. There is significant morbidity associated with a surgical biopsy, thus biopsies are often deferred, and tumors of the brainstem are treated presumptively with radiation and temozolomide. However, in the presence of new targeted therapies, confirming pathology for these patients is becoming increasingly important. We present two cases of IDH-mutant grade 2 astrocytomas of the brainstem that revealed both clinical and radiographic responses to IDH-inhibitor therapy. Interestingly, both patients had the same non-canonical IDH mutation, IDH-R132C, towards which ivosedinib is known to have activity. One patient had tumor progression following radiation therapy and 8 cycles of temozolomide and had subsequently exhibited a dramatic radiographic improvement, including resolution of enhancing disease following initiation of ivosidenib therapy. Clinically, this patient improved from a KPS 50 to KPS 100 after 2.5 years of ivosedinib. The other patient also had an impressive clinical improvement after only 3 months of ivosedinib treatment, with radiographic stability, improvement in balance, and resolution of his previous refractory nausea. These case reports suggest that consideration should be given to brainstem biopsy in adults specifically to evaluate for the presence of a targetable IDH mutation.

RADT-15. THE ROLE OF STEREOTACTIC RADIOSURGERY IN WHO GRADE II MENINGIOMAS: RESULTS FROM A LARGE EUROPEAN MULTICENTER STUDY

Abstract BACKGROUND This study evaluates the outcomes of WHO grade II meningiomas treated with stereotactic radiosurgery (SRS) using a large, multi-institutional European database. We aim to investigate the long-term tumor control rate and morbidity associated with SRS. METHODS Data from 355 consecutive patients treated between 1992 and 2022 at 16 European radiosurgery centers were retrospectively analyzed. After excluding 40 patients due to loss to follow-up, results from 315 patients were included. Clinical and imaging data were independently collected by each center and uniformly entered into a multicenter database. RESULTS The median age of patients was 56 years, with 54% being female. The median follow-up duration was 46.3 ± 36.9 months. Tumors had prior surgical treatment and biopsy in 99% and 1% of cases, respectively. Tumors received previous radiotherapy or SRS in 27.4% of cases. SRS was performed due to local progression in 89.6% of cases, residual tumor in 6.4%, and distant progression in 4.0%. SRS characteristics included a median target volume of 5.1 cm³ and a median margin dose of 16 Gy (53.5% isodose). The 3-year local control rate was 72.0%, with a progression-free survival rate of 66.6% and an overall survival rate of 89.7%. Transient and permanent morbidity rates were 6.4% and 3.5%, respectively. Multivariate analysis identified previous radiotherapy and age as significant factors influencing these outcomes. CONCLUSIONS This study is the largest to date on SRS in WHO grade II meningiomas. Our data shows that SRS is a viable and safe treatment option for residual and recurrent WHO grade II meningiomas

BIOM-19. METHYLATION PROFILING OF PLASMA CELL-FREE DNA IN PEDIATRIC BRAIN TUMOR PATIENTS

Abstract BACKGROUND Circulating tumor DNA (ctDNA) assays are being evaluated to inform clinical decisions in cancer care in adult patients, but the study in pediatric brain tumor patients is rare partly due to very low levels of ctDNA in blood. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. The aim of this study is to utilize methylomes from plasma ctDNA for non-invasive diagnosis in pediatric brain tumor patients. METHODS Using cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), which with low input DNA requirement, we measured methylation profiles of plasma samples from 77 pediatric brain tumor patients and 16 patients with non-neoplastic diseases like epilepsy. Binomial GLMnet classifiers of tumor or tumor subtype were built, in 2000 iterations of 60% training sets. Performance was evaluated in 40% test sets. RESULTS. These 77 pediatric brain tumor patients were a mixture of the most common pediatric brain tumors, include circumscribed astrocytic gliomas (N=23), glioneuronal tumors (N=16), embryonal tumor (N=9), ependymal tumor (N=7), pediatric type diffuse high grade glioma (N= 5), glioma NOS (N=4), mesenchymal tumor (N=4) and other pediatric brain tumors (N=9). The methylation profile differentiated brain tumors from non-neoplastic diseases with 82.9% accuracy (precision = 92.6%, sensitivity = 86.2%, specificity = 66.7 %). For subtype analysis, the methylation profile detected circumscribed astrocytic glioma from non-neoplastic diseases with 85.7% accuracy (precision = 87.5%, sensitivity = 87.5 %, specificity = 83.3 %), and glioneuronal tumors from non- neoplastic diseases with 83.3% accuracy (all precision, sensitivity, and specificity = 83.3 %). CONCLUSIONS The results suggest that methylation profiling of plasma cell-free DNA has the potential to discriminate between pediatric brain tumor patients and patients with non- neoplastic diseases. Larger population cohorts to train even more accurate classifiers will be needed.

NIMG-33. HIGH-RESOLUTION SODIUM MRI OF HUMAN GLIOMAS AT 3T USING PHYSICS-BASED GENERATIVE AI

Abstract BACKGROUND Sodium neuroimaging is a promising technique for diagnosing and monitoring brain tumors, providing insights into microenvironment and metabolism. However, at 3T, it is limited by low signal-to-noise ratio and resolution, resulting in long acquisition times and low-quality images. To address these limitations, we developed a physics-informed generative adversarial network (GAN) approach for high-resolution sodium neuroimaging of brain tumors at 3T. METHODS 5,078 anatomical sequences from 1,330 brain tumor patients undergoing routine proton MRI were used to create a synthetic dataset with physics-based simulated artifacts, including B0 magnetic susceptibility artifacts, chemical shift artifacts, Nyquist aliasing artifacts, Gibbs artifacts, and low-resolution images, with Rician noise added during training to augment the dataset. By using multiple proton MRI contrasts, we hypothesized that the GAN model would learn to correct artifacts while preserving the inherent contrast information. We employed a transfer learning approach with a modified Pix2PixGAN architecture and an Attention-R2UNet generator. Twenty glioma patients consented to participate in this IRB-approved prospective study. Sodium and proton MRIs were acquired in the same sessions using a 3T Siemens scanner using a dual-tuned head coil, with a 3D spoiled gradient-echo sequence optimized for short TE. Sodium-proton exchanger (NHE1) expression was tested with immunohistochemistry from image-guided surgical biopsies. RESULTS High-resolution synthetic-sodium MR images were generated using the GAN model. The proposed method successfully reconstructed high-resolution synthetic-sodium MR images with improved SNR compared to traditional sodium images. Synthetic and native measurements were strongly correlated (R2=0.8539, P<0.0001). A significant correlation was seen between synthetic-sodium MR measurements and relative NHE1 tissue expression (ρ=0.5817, P=0.0036). CONCLUSION Results suggest that high-resolution synthetic-sodium MRI retains much of the inherent information from native sodium MR while accurately representing NHE1 expression. This approach could make high-resolution sodium neuroimaging at 3T feasible in the clinical environment, potentially improving diagnosis, monitoring, and treatment of brain tumors.

Multi-bioinformatics revealed potential biomarkers and repurposed drugs for gastric adenocarcinoma-related gastric intestinal metaplasia

Biomarkers associated with the progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA), i.e., GA-related GIM, could provide valuable insights into identifying patients with increased risk for GA. The aim of this study was to utilize multi-bioinformatics to reveal potential biomarkers for the GA-related GIM and predict potential drug repurposing for GA prevention in patients. The multi-bioinformatics included gene expression matrix (GEM) by microarray gene expression (MGE), ScType (a fully automated and ultra-fast cell-type identification based solely on a given scRNA-seq data), Ingenuity Pathway Analysis, PageRank centrality, GO and MSigDB enrichments, Cytoscape, Human Protein Atlas and molecular docking analysis in combination with immunohistochemistry. To identify GA-related GIM, paired surgical biopsies were collected from 16 GIM-GA patients who underwent gastrectomy, yielding 64 samples (4 biopsies per stomach x 16 patients) for MGE. Co-analysis was performed by including scRNAseq and immunohistochemistry datasets of endoscopic biopsies of 37 patients. The results of the present study showed potential biomarkers for GA-related GIM, including GEM of individual patients, individual genes (such as RBP2 and CD44), signaling pathways, network of molecules, and network of signaling pathways with key topological nodes. Accordingly, potential treatment targets with repurposed drugs were identified including epidermal growth factor receptor, proto-oncogene tyrosine-protein kinase Src, paxillin, transcription factor Jun, breast cancer type 1 susceptibility protein, cellular tumor antigen p53, mouse double minute 2, and CD44.

Ultrasound-guided core-needle biopsy for extra-ocular orbital soft tissue tumours: a minimally invasive alternative to surgical biopsy

PurposeTo assess the feasibility, accuracy, and safety of ultrasound (US)-guided coaxial core-needle biopsy (CNB) for histomolecular diagnosis of extra-ocular orbital soft tissue tumours as a minimally invasive alternative to surgical biopsy. MethodsThis retrospective study was conducted at a single Comprehensive Cancer Center and included all consecutive patients referred to our center between 2015 and 2023 for the diagnosis and treatment of orbital soft tissue tumours. All patients underwent US-guided transconjunctival coaxial CNB using a semiautomatic 18-gauge biopsy gun. Pathological analysis included morphological analysis, immunostainings, and molecular biology techniques when required. ResultsA total of 26 patients were included consisting of 21 adults (median age: 64 years, range: 24-93 years), 1 adolescent (17 years), and 4 children (aged 4 weeks, 5 weeks, 26 months, and 6 years). Tumour largest diameters ranged from 11 to 57 mm (median 23 mm). The overall feasibility of CNB was 88% (23/26), and it was 100% (5/5) in children. The histological accuracy was 91% (21/23), and its safety was 96% (25/26). Molecular biology analyses were requested in 9 out of 23 cases and were successful in all instances. The final diagnoses included hematological malignancies (n = 8), carcinomas (n = 5), metastases (n = 4), sarcomas (n = 4), and benign mesenchymal tumours (n = 5). ConclusionsThis study supports the use of US-guided coaxial CNB for the pathological and molecular diagnosis of orbital soft tissue tumours in both children and adults. This technique shows promise as a minimally invasive alternative to open surgical biopsy.

Role of Image-Guided Biopsy in Nonpalpable Breast Lesions: A Study in the Sub-Himalayan Region of North India

Background Nonpalpable breast lesions pose a challenge in their early diagnosis. Image-guided biopsy is preferred in these cases so that a pathological diagnosis of breast carcinoma is reached timely for a better prognosis as the disease has an increased chance of successful outcome with early identification and treatment. Objective The study aims at evaluating the role of stereotactic core needle biopsy (CNB) and percutaneous ultrasound-guided core needle biopsy (US-CNB) in diagnosing suspicious nonpalpable breast lesions. Methods Our study included 35 patients with nonpalpable breast lesions and having a Breast Imaging Reporting and Data System (BI-RADS) risk assessment category IV or V on mammography or sonography. These 35 lesions were subjected to percutaneous image-guided (stereotactic or US) biopsy for histopathological analysis. Results Out of a total of 35 cases, 17 were pathologically malignant (48.6%), with the most common subtype being invasive ductal carcinoma (82.3%). Twenty-nine cases underwent US-CNB, 16 (55.1%) of which were malignant and 13 (44.8%) were benign on histopathological evaluation (HPE). The remaining six cases, which on mammography showed no mass but suspicious malignant calcification only, were subjected to stereotactic CNB, out of which one (16.6%) was malignant and five (83.3%) were benign on HPE. Hence, the lesions visible on sonography were more likely to be malignant. Conclusion Sonography and mammography play a complimentary role in detecting breast carcinoma. Percutaneous biopsy under image guidance can be used as an accurate diagnostic alternative to open surgical excisional biopsy to avoid diagnostic delay.

Fabry cardiomyopathy: myocardial fibrosis, inflammation and reduced mannose6phosphate receptors cause low accessibility to enzyme therapy

Abstract Background Clinical impact of enzyme replacement therapy (ERT) on advanced Fabry disease cardiomyopathy (FDCM) appears limited. Purpose Clarify the pathologic mechanisms responsible of ERT inefficacy in the advanced FDCM. Methods Ten male patients with advanced FDCM (echocardiographic maximal wall thickness 19.3 ± 2.1 mm) underwent left ventricular endomyocardial biopsy before and 4 hours after beta-agalsidase infusion. Comparative studies between pre and post infusion samples included: histology and electron microscopy; assessment of myocardial alpha-galactosidase A activity; immunohistochemistry for alpha-galactosidase A and semiquantitative evaluation (from 0 to 3) of its cardiomyocyte content; Ultrastructural immunogold analysis with anti-alpha-galactosidase A ab. Western Blot (WB) quantification of mannose-6-phosphate receptors (M6Pr). Controls were surgical left ventricular biopsies from patients with mitral stenosis. Results Histologic and Ultrastructural evaluation showed no removal of storage material while myocardial fibrosis was 9.8 ± 6.8 vs 3.8 ± 2.0 of controls and virus-negative lymphocytic inflammation was observed in 7 out of 10 patients. At Ultrastructural immunogold analysis, Myocardial alpha-galactosidase A activity increased in post infusion samples by overall 1.89-fold. Alpha-galactosidase A immunostaining in cardiomyocytes was absent at baseline in all patients and did not significantly improve in post-infusion samples. Immunogold particles increased by 1.33-fold remaining far from normal controls (86.9 ± 6.6). Protein analysis showed M6Pr in advanced FDCM to be 81% lower than in normal heart. Conclusions Our study shows a low accessibility to ERT of cardiomyocytes affected by advanced FDCM. It is sustained by myocardial fibrosis, inflammation and severe down-regulation of M6Pr. Figure Legend Histologic and ultrastructural and mannose6phosphate receptors characteristics of patients with severe Fabry Disease Cardiomyopathy. Panel A shows severe cellular glycolipid infiltration associated with diffuse interstitial fibrosis (Masson trichrome, 100x). Panel B reveals an overlapping lymphocytic CD45Ro+ myocardial inflammation with focal necrosis of adjacent cardiomyocytes. Insert(i), Ultrastructural detail showing vacuoles (black arrows) to consist of myelin bodies,( scale bar=3μm). Panel C (upper) Western blot analysis of all 10 patients of Mannose-6-phosphate Receptor, molecular weight 275 Kd. Alpha sarcomeric actin (43 kDa) was used as a loading control. (Panel C -lower) Panel D: Graphs document western blot of Mannose-6-phosphate Receptor, in all 10 patients with severe FDCM showing 3-fold lower of Mannose-6-phosphate Receptor values in patients versus normal heart (4.830 ± 1116,724 vs 14.737± 1145,386; p < 0.001).

Cardiomyocyte regeneration in human myocarditis

Abstract Background Newly generated cardiomyocytes (NGC) concur to recovery of human myocarditis. Purpose describe NGC’s contribute with age and their modality of myocardial homing and integration. Methods We retrospectively assessed NGC in 213 consecutive patients with endomyocardial biopsy diagnostic for myocarditis, normal coronaries and valves. Tissue samples were processed for histology and immune-histochemistry for CD3+ T lymphocytes, alpha-sarcomeric-actin, junctional connexin-43, Ki-67, phosphorylated STAT3 (p-STAT3) and Western Blot (WB) for HMGB1. Frozen samples were analyzed with polymerase chain reaction (PCR) for cardiotropic viruses. Controls included 20 normal surgical biopsies. NGC were defined as small myocytes (diameter < 10 µ) with nuclear positivity to Ki-67 and p-STAT3, positive immunostaining for cytoplasmic alpha-sarcomeric-actin and connexin 43. Their number/mm2, relation with age and pathway of integration were evaluated. Results PCR was positive for viral genomes in 16% of cases. NGC mean diameter was 6.6 ± 3.34 vs 22.5 ± 3.11 µm adult cells; their number, in comparable LVEF, was 86.3 ± 10.3/mm2 in patients between 10 and 40 years; 50.4 ±13.8/mm2 in those between 41 and 60; 15.1 ± 5.7/ mm2 in those between 61 and 80; control NGC were 0.2± 0.2/mm2 ; NGC were no statistically different in viral and non-viral myocarditis. HMGB1 and STAT-3 were remarkably higher than controls. NGC crossed the membrane and grew integrated within the empty necrotic myocytes. Conclusions NGCs are constantly recognizable in acute human myocarditis. Their number declines with age. Their integration within necrotic myocytes consents preservation of cardiac structure and function.

Frequency and outcomes of new or suspicious MRI findings on breast MRI for patients on neoadjuvant therapy.

To assess the frequency and outcomes of indeterminate enhancing findings on breast MRI unrelated to the index primary tumor(s) in patients on neoadjuvant therapy (NAT). This retrospective review identified all diagnostic breast MRIs performed to evaluate response to NAT at our institution between 2017 and 2020. All exams with indeterminate enhancing findings (BI-RADS 3-5) unrelated to the index tumor(s) for which follow-up imaging or tissue diagnosis was recommended were included. Cases lacking a pre-treatment MRI or those with insufficient follow-up were excluded. Imaging of all post-NAT breast MRIs were re-reviewed. The electronic medical record was reviewed to evaluate patient and lesion characteristics and outcomes. Between 2017 and 2020, 614/4042 (15.2%) breast MRIs were performed to evaluate response to NAT. After exclusions, 38 of these exams (6.2%) identified 42 indeterminate enhancing findings unrelated to the index tumor for which follow-up imaging (15 exams) or tissue diagnosis (23 exams) was recommended. Fifteen of 42 (35.7%) of the findings were new compared to the pre-treatment baseline MRI, 8/42 (19.0%) increased and 19/42 (45.2%) were present on pre-treatment MRI. Most findings were contralateral to the index tumor (28, 66.7%). Findings were masses (17, 40.4%), focus (15, 35.7%), and non-mass enhancement (10, 23.8%). Of the 42 findings, 19 (45.2%) underwent percutaneous biopsy, 10 (23.8%) underwent surgical biopsy or mastectomy, and 13 (31%) were followed by imaging. Thirty-seven were benign, 4 were high-risk lesions without upgrade (atypical ductal hyperplasia, atypical lobular hyperplasia, and papillomatosis with atypical ductal hyperplasia), and one (2.4%) was malignant (invasive lobular carcinoma), which was non-mass enhancement present on the pre-treatment MRI. Indeterminate enhancing lesions unrelated to the index tumor(s) on breast MRIs performed to assess response to neoadjuvant chemotherapy are uncommon. When present, these lesions have an extremely low likelihood of malignancy, especially when new compared to the pre-treatment MRI. Because incidental indeterminate enhancing lesions on breast MRI at post-NAT follow-up are rarely malignant, radiologists should be judicious in recommending follow-up or tissue diagnosis for such lesions after NAT.

Risk Factors Associated with Progression to Surgery in Patients with Ischemic Colitis.

Ischemic colitis (IC), the most common ischemic syndrome affecting the gastrointestinal tract, results from a decreased blood supply to the colon. Persistent symptoms can lead to complications, necessitating surgery. This study assessed the clinical characteristics and risk factors for poor outcomes in IC. This retrospective observational study examined the medical records of 141 patients diagnosed pathologically with IC via surgery or colonoscopy at Chonnam National University Hwasun Hospital between April 2004 and August 2023. Eighteen (12.8%) and 123 (87.2%) patients were diagnosed by surgical biopsy and biopsy with colonoscopy, respectively. Multivariate analysis identified right-sided colon involvement, fever, and the absence of hematochezia as risk factors for the progression to surgery (odds ratio [OR]=5.924, 95% confidence interval [CI] 1.009-34.767, p=0.049; OR=24.139, 95% CI 5.209-111.851, p<0.001; and OR=0.076, 95% CI 0.013-0.446, p=0.004, respectively). The in-hospital mortality was 5.7% (8/141), and the patients who died exhibited higher rates of shock. The median (interquartile range) hospital stay was 11 (1-219) days. Patients who had longer hospital stays (≥14 days) had a significantly higher rate of fever but a lower rate of hematochezia. A multidisciplinary approach is crucial for determining the need for surgery in patients with right-sided colon involvement, fever, or the absence of hematochezia.

Multiple Liver and Jejunal Abscesses Due to Fasciola Flat Worm: An Uncommon Case Report from Iran.

Fascioliasis is a zoonotic condition precipitated by the trematode known as Fasciola spp. This parasite affected almost 2.4 to 17million individuals in the world. The occurrence of liver abscesses is an infrequent phenomenon, potentially arising as a secondary outcome of cholangitis or hepatic inflammation. In this study, we have reported a case of a hepatic abscess induced by Fasciola spp. A 29-year-old male presented with generalized abdominal discomfort, primarily concentrated in the right upper quadrant, which had progressively worsened over the past seven months. The patient did mention a weight loss of approximately 10kg during the course of their illness, along with increasing fatigue. Eosinophilia was seen too (35%). The stool exam test was negative. An enteroscopy was conducted, revealing no pathological abnormalities. Following this, the surgeon prescribed a surgical biopsy of the mass, which yielded a diagnosis of multiple eosinophilic granulomatous abscesses within the jejunal wall and mesentery. The Fasciola IgG test returned a positive result. After of follow-up, the patient fully recovered. Fascioliasis should be considered in the differential diagnoses of liver abscesses. Because of earlier diagnosis, can be avoided of invasive diagnostic tests and therapeutic interventions can be started earlier.